1 The 3 genomic paradoxes 3c K N C

2 K-value paradox: Complexity does not correlate with chromosome number Ophioglossum reticulatumHomo sapiensLysandra atlantica ~1260

3 C-value paradox: Complexity does not correlate with genome size. 3.4  10 9 bp Homo sapiens 6.8  bp Amoeba dubia 1.5  bp Allium cepa

4 N-value paradox: Complexity does not correlate with gene number. ~21,000 genes ~25,000 genes ~60,000 genes

5 Possible solutions:

6 What is complexity?

7 Solution 1 to the N-value paradox: Many protein-encoding genes produce more than one protein product (e.g., by alternative splicing or by RNA editing).

8 RNA editing Alternative splicing

9 The combinatorial use of RNA editing and alternative splicing probably causes the human proteome to be 5-10 times larger than that of Drosophila or Caenorhabditis.

cells 1,031 cells 19,000 genes 13,600 genes ~10 8 cells

11 Solution 2 to the N-value paradox: We are counting the wrong things, we should count other genetic elements (e.g., small RNAs).

12 Solution 3 to the N-value paradox: We should look at connectivity rather than at nodes.

13 L. Mendoza and E. R. Alvarez-Buylla Dynamics of the genetic regulatory network for Arabidopsis thaliana flower morphogenesis. J. Theor. Biol. 193:

14 Solution 4 to the N-value paradox: The numbers provided by the various genome annotations are wrong!

15 Comparison of three databses Hogenesch JB, Ching KA, Batalov S, Su AI, Walker JR, Zhou Y, Kay SA, Schultz PG, & Cooke MP A comparison of the Celera and Ensembl predicted gene sets reveals little overlap in novel genes. Cell 106:

16 Range of C-values in various eukaryotic taxa _______________________________________________________________ Taxon Genome size range Ratio (Kb) (highest/lowest) _______________________________________________________________ 298,261 Eukaryotes 2, ,000, ,261 Amoebae 35, ,000,000 19,433 Fungi 8, ,470, Animals 49, ,000,000 2,837 Sponges 49, ,900 1 Molluscs 421, ,290, Crustaceans 686, ,100, Insects 98, ,350, Bony fishes 340, ,000, Amphibians 931, ,300, Reptiles 1,230, ,340,000 4 Birds 1,670, ,250,000 1 Mammals 1,700, ,700,000 4 Plants 50, ,000,000 6,140 _______________________________________________________________

17 If the variation in C-values is attributed to genes, it can be due to interspecific differences in (1) the number of protein-coding genes (2) the size of proteins (3) the size of protein-coding genes (4) the number and sizes of genes other than protein-coding ones.

18 The number of protein- coding genes in eukaryotes is thought to vary over a 50- fold range. This variation is insufficient to explain the 300,000-fold variation in nuclear-DNA content.

19

20 The bigger the genome, the smaller the genic fraction

21 Nongenic DNA is the sole culprit for the C-value paradox!99.998%

22 MECHANISMS FOR GLOBAL INCREASES IN GENOME SIZE Genome increase: (1) global increases, i.e., the entire genome or a major part of it is duplicated (2) regional increases, i.e., a particular sequence is multiplied to generate repetitive DNA.

23 Polyploidization = the addition of one or more complete sets of chromosomes to the original set. An organism with an odd number of autosomes cannot undergo meiosis or reproduce sexually. Musa acuminata

24 allopolyploidy

25 Triticum urartu (AA)  Aegilops speltoides (BB) T. turgidum (AABB)  T. tauschii (DD) ` T. aestivum (AABBDD)

26 autopolyploidy

27 Following polyploidization, a very rapid process of duplicate-gene loss ensues.

28 Allohexaploid Triticum aestivum originated about 10,000 years ago. In this very short time, many of its triplicated loci have been silenced. The proportion of enzymes produced by triplicate, duplicate, and single loci is 57%, 25%, and 18%, respectively.

29 During evolution autopolyploidy & allopolyploidy becomes cryptopolyploidy.

30 Genome sizes in 80 grass species (Poaceae).

31

32

33 It has been suggested that the emergence of vertebrates was made possible by two rounds of tetraploidization. Two cryptooctoploids?

34 Does chromosome number increase due to polyploidy affect the phenotype? Chrysanthemum species have 9 to 90 chromosomes in haploid cells.

35 54 duplicated regions.

36 2 possible explanations: (1) the duplicated regions were formed independently by regional duplications occurring at different times. (2) the duplicated regions have been produced simultaneously by a single tetraploidization event, followed by genome rearrangement and loss of many redundant duplicates.

37 50/54 duplicated regions have maintained the same orientation with respect to the centromere. 54 independent regional duplications are expected to result in ~7 triplicated regions (i.e., duplicates of duplicates), but none was observed.

38 Loss of 92% of the duplicate genes. Occurrence of map disruptions.

39 Arabidopsis thaliana: regional duplications

40 What about polysomy?

41 Polysomy is usually deleterious. trisomy 21

42 An exception?

43 MAINTENANCE OF NONGENIC DNA: HYPOTHESES (1) The selectionist hypothesis. (2) The neutralist hypothesis (junk DNA). (3) The intragenomic selectionist hypothesis (selfish DNA). (4)The nucleotypic hypothesis.

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45

46

47

log nuclear volume (  m 3 ) log DNA per cell () Correlation between nuclear volume and nuclear DNA content in apical meristem cells of 30 herbaceous species. Regression slope = fitted by least squares.

49

50 MAINTENANCE OF NONGENIC DNA: EVIDENCE (1) The selectionist hypothesis. (2) The neutralist hypothesis (junk DNA). (3) The intragenomic selectionist hypothesis (selfish DNA). (4)The nucleotypic hypothesis.

51 Even whole chromosomes may be junk. A person needs an Y, like a fish needs bicycles.

52 with apologies to Irina Dunn, Australian feminist (1970).

53 Nature (2004) 431: